The focus of this project is the investigation of immune tolerance in an in vivo model using T cell receptor transgenic mice. Our laboratory has developed an experimental model of T cell tolerance induced by bacterial superantigens in transgenic mice. Because all T cells in the transgenic mice express the Vbeta8.2 transgene, tolerization with the SEB superantigen affects all of the T cells. Following tolerization, we have demonstrated that immune responses are inhibited in an antigen specific manner. WE have transferred the Vbeta8.2 transgene into SJL mice and demonstrated that they respond to the immunodominant T cell epitope of myelin basic protein, mimicked by the synthetic peptide spanning amino acids 89-101 of myelin basic protein, which is the auto-antigen in this disease. Using this model of autoimmune disease, we will investigate the mechanisms of T cell tolerance and clonal anergy in peptide specific autoimmune responses modulated by tolergenic doses of the superantigen SEB. In addition, we will construct alphabeta T cell receptor transgenic mice which specifically recognize a synthetic peptide epitope. These transgenic mice will be used to investigate the mechanism of peptide specific tolerance in vivo.